The anti-ictogenic effects of levetiracetam are mirrored by interictal spiking and high-frequency oscillation changes in a model of temporal lobe epilepsy

Abstract

PurposeMesial temporal lobe epilepsy (MTLE) is the most prevalent type of partial epileptic disorders. In this study, we have analyzed the impact of levetiracetam (LEV) in the pilocarpine model of MTLE. MethodsSprague-Dawley rats (n=19) were injected with pilocarpine (380mg/kg, i.p.) to induce a status epilepticus. Twelve animals were used as controls and seven were treated with LEV. They were implanted with bipolar electrodes in the CA3 subfield of the hippocampus, entorhinal cortex (EC), dentate gyrus (DG) and subiculum and EEG-video monitored continuously from day 4 to day 14 after SE. ResultsOnly 29% of LEV-treated animals had seizures compared to all controls following a latent period that was similar in duration. Seizure rates were lower in LEV-treated animals. In LEV-treated animals without seizures, lower interictal spike rates were found in all regions compared to controls. Analysis of interictal high-frequency oscillations (HFOs) revealed that LEV-treated animals without seizures had lower rates of interictal spikes with ripples (80–200Hz) in CA3, EC and subiculum (p<0.01), whereas rates of interictal spikes with fast ripples (250–500Hz) were significantly lower in CA3 and subiculum, compared to controls. ConclusionOur findings indicate that the anti-ictogenic properties of LEV are mirrored by decreases of interictal spike rate in temporal lobe regions, and are accompanied by subregion-specific decreases of HFO occurrence in CA3 and subiculum. Overall, this evidence suggest that LEV may inhibit neural network activity in regions that are known to play important roles in MTLE.